Preparation of high specific activity 86Y using a small biomedical cyclotron

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Abstract

86Y is an attractive PET radionuclide due to its intermediate half-life. 86Y was produced via the 86Sr(p,n)86Y nuclear reaction. Enriched SrCO3 or SrO was irradiated with 2-6 μA of beam current for <4 h on a CS-15 cyclotron. It was shown that the SrO target could withstand at least 6 μA of beam current, a significant improvement over a maximum of 2 μA on the SrCO3 target. Average yields of 4.5 mCi/μA·h were achieved with SrO, which represent 71% of the theoretical yield, compared to 2.3 mCi/μA·h with SrCO3. The radioisotopic contaminants were 86mY (220%), 87Y (0.27%), 87mY (0.43%) and 88Y (0.024%). 86Y was isolated in an electrochemical cell consisting of three Pt electrodes. The solution was electrolyzed at 2000 mA (40 min) using two Pt plate electrodes. A second electrolysis (230 mA for 20 min) was performed using one Pt plate and a Pt wire. On average, 97.1% of the 86Y was recollected on the Pt wire after a second electrolysis. The 86Y was collected from the Pt wire using 2.8 M HNO3/EtOH (3:1). After evaporation, 86Y was reconstituted in 100 μl of 0.1 M HCl. Target materials were recovered as SrCO3 and then converted to SrO by thermal decomposition at 1150°C. Specific activity of 86Y was determined to be 29±19 mCi/μg via titration of 86Y(OAc)3 with DOTA or DTPA. We have established techniques for the routine, economical production of high purity, high specific activity 86Y on a small biomedical cyclotron that are translatable to other institutions.

Introduction

Yttrium-90 (t1/2=64.1 h, β=100%, Eβ–=1.3 MeV) is one of the most widely used radionuclides for therapy with radiolabeled antibodies [1], [2]. Zevalin, an anti-CD20 monoclonal antibody radiolabeled with 90Y, used for the treatment of non-Hodgkin lymphoma, was the first FDA-approved radioimmunotherapy radiopharmaceutical [3]. However, because Y-90 emits only β particles, accurate dosimetry is difficult. Due to the similar coordination chemistries of In(III) and Y(III), 111In (t1/2=2.83 days, γ-ray 171, 245 keV) has routinely been used as an imaging surrogate for 90Y for dosimetry determinations [4], [5]. However, there is concern about different in vivo stabilities of the complexes associated with these two radioisotopes [6], and the biodistribution patterns of these two metal ions are reported to be dissimilar [7], [8], [9]. Therefore, the positron-emitting 86Y (t1/2=14.7 h, β+=33%, Eβ+=1.2 MeV) has been proposed for use as a quantitative PET imaging agent for in vivo determination of biodistribution and dosimetry of therapeutic 90Y pharmaceuticals for individual patients [10], [11], [12], [13].

Yttrium is bound by commonly used bifunctional chelators such as 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA) and diethylenetriaminepentaacetic acid (DTPA) [14], [15], [16], [17], [18], which makes 86Y an attractive PET radionuclide for labeling biomolecules [8], [19], [20]. 86Y is also an intermediate half-lived positron-emitting radionuclide like 64Cu (t1/2=12.7 h, β+=17.9%, Eβ+=0.6 MeV), which would enable PET imaging beyond 24-h postinjection. In contrast to the copper(II) ion, yttrium prefers the +3 oxidation state for making a neutral complex with the conjugated DOTA ligand. It has been reported that the Y-DOTA chelate demonstrates higher in vivo stability than the Cu analog, resulting in lower nontarget and clearance tissue accumulation [21].

86Y can be produced by the 86Sr(p,n)86Y reaction using a small biomedical cyclotron. 86Y has been previously separated from target solutions by cation-exchange chromatography followed by coprecipitation of 86Y with La(III) [22] or Fe(III) [23]. However, these original methods are multistep separations and require the addition of carrier, and so more efficient no-carrier added ion-exchange methods using a Sr/Y-selective resin have recently been reported [9], [24]. In 2002, Reischl et al. [25] reported that simple electrolysis can provide high purity 86Y in a short time. In all cases, enriched [86Sr]SrCO3 was employed as the target material [9], [22], [23], [24], [25]. The aim of this study was to produce high purity 86Y in an efficient, cost-effective manner for routine use and supply by adaptation of previously reported methods.

Herein, we report that a different chemical form of enriched 86Sr is a superior target material and produces higher yields of 86Y. Detailed descriptions of the electrochemical separation procedures are also presented.

Section snippets

General

Isotopically enriched SrCO3 and SrO (96.4% each) were bought from Trace Sciences International (Richmond Hill, Ontario, Canada). High purity reagents used in the electrochemical separation and recycling experiments (99.999999% HCl, 99.9999% HNO3, 99.99% ammonium hydroxide, 99.999% ammonium nitrate, 99.999% ammonium carbonate) were purchased from Alfa Aesar (Ward Hill, MA). Ethanol was purchased from AAPER Alcohol and Chemical (Shelbyville, KY), and DOTA and DTPA were purchased from Strem

Production of 86Y with enriched 86Sr materials

As stated, two different solid targets were used in this study. The best results were obtained using a Pt disk and enriched SrO as the target material, because both are more stable to high temperature and to acid than the Al and SrCO3 alternatives.

During the initial production runs, an aluminum disk was used with SrCO3 as the target material. However, pressing the target material into the disk's depression was insufficient to stabilize the material during bombardment, and a cap had to be

Conclusion

In summary, 86Y was produced in the highest yield using a small amount of [86Sr]SrO as the target material. SrO was a more effective target than commonly used SrCO3 because of its thermal stability. 86Y was separated in high collection yield by electrodeposition and by using two platinum plates and one platinum wire. The use of NH4NO3 as electrolyte during the first electrolysis stabilized the pH of the electrocell. The 86Y activity adsorbed on Pt wire and was collected in high yield using a

Acknowledgments

This work was supported by the National Cancer Institute (NCI R24 CA86307) and the United States Department of Energy (DE-FG02-87ER60512). The authors would like to thank Bill Margenau, Pat Margenau and Grainne Biddlecombe for cyclotron operation and technical support.

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  • Cited by (0)

    This work was supported by a grant from the U.S. Department of Energy (grant DE FG02-87ER60512). The production of yttrium-86 at Washington University is supported by a grant from the National Cancer Institute (grant R24 CA86307).

    1

    Current address: Department of Molecular Medicine, Kyungpook National University School of Medicine, 101 Dongin-dong 2-ga, Joong-gu, Daegu 700-422, Korea.

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